A novel method is presented using N-N ylides (prepared by in situ amination of a tertiary amine) for the aziridination of a range of enone systems. The amine may be used sub-stoichiometrically, and promising levels of enantioselectivity are observed with quinine as promoter. [reaction: see text].

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The design of new chiral catalysts for enantioselective synthesis of all-carbon quaternary stereogenic centers is a critical and challenging objective in modern chemistry.[1] Such catalysts must be enantio-differentiating but also especially active because the desired reactions involve additions of carbon nucleophiles to sterically congested electrophilic sites. Herein, we disclose a readily available chiral N-heterocyclic carbene (NHC) that can be used to promote the catalytic asymmetric conjugate addition (ACA) [2] of organozinc reagents to cyclic g-keto esters [Eq. (1)]; these transformations give rise to the enantioselective formation of all-carbon quaternary stereogenic centers that bear a readily functionalizable carboxylic ester substituent in up to 95 % ee. [3][4][5] In nearly all of the catalytic ACA reactions (one exception), the new chiral NHC (Cu complex generated in situ) delivers significantly higher efficiency and asymmetric induction than the previously reported systems.We began our investigation by examining the ability of Cu complexes generated from the reaction of 1[5a] and 2[5c](Scheme 1) with (CuOTf) 2 ·C 6 H 6 in promoting the ACA of Me 2 Zn to five-and six-membered ring g-keto esters 4 and 5 (Table 1). With cyclopentenone 4 a as the substrate and in the presence of binaphthyl-based 1 and (CuOTf) 2 ·C 6 H 6 (2.5 mol %), less than 10 % conversion is detected after 24 h (Table 1, entry 1). When biphenyl complex 2 is used, there is only 15 % conversion and 6 is formed in 30 % ee (Table 1, entry 2). With six-membered ring enone 5 a, Cu-based complexes derived from 1 and 2 (Table 1, entries 4-5) promote the ACA of Me 2 Zn more efficiently (60 % and > 98 % conversion) and with improved enantioselectivity (73 % ee and 33 % ee), but only in comparison to the reactions of cyclopentenone 4 a and not at synthetically useful levels. Faced with the inferior activity and asymmetric induction provided by the Cu complexes of 1 and 2, we set out to identify a more effective chiral catalyst. This initiative led us to discover that complex 3,[6] a sulfonate-containing chiral NHC (Table 1, entry 3), promotes the addition of Me 2 Zn to 4 a with substantially higher efficiency (> 98 % conversion, 17 h versus < 15 % conversion with 1 and 2) and superior enantioselectivity (84 % ee versus 30 % ee with 1 and 2). Furthermore, catalytic ACA of Me 2 Zn to cyclohexenone 5 a proceeds efficiently with the Cu complex generated in situ from 3, which affords 7 in 75 % ee. Thus, in one case (compare Scheme 1. Previously reported 1 and 2 and the new chiral NHC complex 3.

Compared with statin monotherapy, ezetimibe with statin therapy was cost-effective for secondary prevention of CHD and stroke and for primary prevention of these conditions in patients whose LDL-C levels are ≥100 mg/dL and in patients with diabetes, taking into account a 90% cost reduction for ezetimibe.